digoxin and Hyperaldosteronism

Topics: Adrenocorticotropic Hormone; Aldosterone; Angiotensins; Desoxycorticosterone; Digoxin; Dogs; Heart Failure; Hyperaldosteronism; Hypertension; Hypertension, Renal; Kidney; Liver Cirrhosis; Metabolism; Nephrosis; Physiology; Renin; Research; Sodium

A 44-year-old woman was admitted to our hospital due to severe hypertension. An electrocardiogram (ECG) and an echocardiogram showed severe left ventricular hypertrophy. Her plasma aldosterone level was elevated. Magnetic resonance imaging revealed a small mass in the right adrenal gland. Before removal of the tumor, plasma endogenous digitalis-like substance (EDLS) levels were elevated. After removal of the tumor, EDLS levels quickly returned to the normal level. A series of echocardiograms and ECGs over a 6- year period after removal of the tumor showed marked regression of cardiac hypertrophy. These findings suggest that EDLS may be closely related to the development of concentric cardiac hypertrophy in primary aldosteronism.

Topics: Adrenal Gland Neoplasms; Adult; Cardenolides; Digoxin; Echocardiography; Electrocardiography; Female; Humans; Hyperaldosteronism; Hypertension; Hypertrophy, Left Ventricular; Saponins

To evaluate the importance of an endogenous sodium pump inhibitor in the pathogenesis of low renin human hypertension, the urinary excretion of a digoxin-like immunoreactive substance (DLIS) was measured in eight patients with primary aldosteronism (n = 5, with adenomas) during two sequential 1-week periods of low- (20 mmol/l NaCl) and high- (200 mmol/l NaCl) sodium intake. DLIS excretion increased consistently during high-sodium intake while urinary aldosterone, plasma renin activity, cortisol and adrenocorticotropic hormone did not change. Although blood pressure showed a time-course parallel to that of the urinary DLIS, the blood pressure increments were not accompanied by evidence of vasoconstriction since forearm blood flow (plethysmographic technique) increased and forearm vascular resistances were reduced. Moreover, the reactivity of forearm arterioles to local norepinephrine was unchanged during the period of low- and high-salt intake, despite the fact that an endogenous sodium pump inhibitor should, supposedly, sensitize the responses to an adrenergic agonist. Finally, forearm vasoconstrictor responses to ouabain, a pharmacological Na+,K(+)-ATPase antagonist, were potentiated during the high-salt diet, a result not expected if an increased number of sodium pumps were occupied by an endogenous inhibitor. These results provide unequivocal evidence for a modulation by salt intake of the urinary excretion of a DLIS in patients with primary aldosteronism. This substance might participate in the regulation of body fluid volume in this syndrome and possibly in other physiological conditions. However, no evidence could be found for a cause--effect relationship between blood pressure and DLIS increments during high-salt intake, at least during the short-term course of the study.

Topics: Aldosterone; Blood Pressure; Blood Proteins; Cardenolides; Digoxin; Electrolytes; Forearm; Hematocrit; Hemodynamics; Humans; Hydrocortisone; Hyperaldosteronism; Norepinephrine; Ouabain; Saponins; Sodium-Potassium-Exchanging ATPase; Sodium, Dietary; Vascular Resistance; Vasoconstriction

Plasma from 37 essential hypertensive patients, from 11 subjects with primary aldosteronism and from 23 normotensive subjects was tested for ouabain-like activity. Despite a very substantial overlap, hypertensive patients (both essential and secondary) showed significantly higher levels of a ouabain-like plasma factor compared to normotensive controls. No substantial differences could be detected, however, between the two forms of hypertension; in particular, no significant changes were observed in the low-PRA subgroup. Our results are hardly compatible with the hypothesis that this substance may be of crucial importance in the development either of essential hypertension or of primary aldosteronism.

Topics: Adolescent; Adult; Aged; Blood Pressure; Cardenolides; Digoxin; Female; Glomerular Filtration Rate; Humans; Hyperaldosteronism; Hypertension; Male; Middle Aged; Ouabain; Protein Binding; Renin; Saponins; Sodium-Potassium-Exchanging ATPase

Red cell sodium (RBC-Na+) concentrations were measured using 23Na nuclear magnetic resonance (NMR), without the destruction of erythrocyte membranes. Subjects were categorized into four groups: 20 normotensive subjects (NT group), 20 age-matched essential hypertensive patients (EHT group), 10 patients with primary aldosteronism (PA group), and 18 patients treated with digoxin (DIG group). Although RBC-Na+ concentrations were similar between the NT group (6.14 +/- 0.80 (Mean +/- SD) mmol/l) and the EHT group (5.92 +/- 0.99), they were significantly higher in both the PA group (7.55 +/- 0.88, p less than 0.001) and the DIG group (8.43 +/- 3.81, p less than 0.02). In the PA group, RBC-Na+ concentrations decreased significantly after resection of the adenoma, and there was an inverse relationship between serum potassium and RBC-Na+ concentrations (r = -0.65, p less than 0.01). In the DIG group, RBC-Na+ concentrations tended to increase in proportion to serum digoxin levels (r = 0.53, p less than 0.05). These results support the view that RBC-Na+ concentrations are determined primarily by Na+/K+-pump activity of red cell membranes. This study showed also that Na+ NMR is an useful method determining intracellular Na+ concentrations.

Topics: Digoxin; Erythrocytes; Female; Humans; Hyperaldosteronism; Hypertension; Magnetic Resonance Spectroscopy; Male; Potassium; Sodium

New method for measuring plasma and urinary Na-K-ATPase inhibitor (ATPI) was developed. Plasma and urine were extracted with reversed phase cartridge column and sample was reconstituted by assay buffer. Na-K-ATPase inhibitory activity of sample was monitored by continuously recording the absorbance of NADH at 340 nm, which coupled to the dephosphorylation of ATP. Ouabain was used for standards of Na-K-ATPase inhibition and this standard showed good linearity ranged 5-100 nmol/ml. Using this new method, P-ATPI and U-ATPI were quantitatively evaluated and paradoxical Na-K-ATPase stimulating phenomenon which observed in conventional method (Hamlyn et al) was diminished. Adopting of this new method for measuring plasma(P-) and urinary(U-)ATPI, and radioimmunoassay for P- and U-digitalis-like substance(DLS)--using crossreactivity to anti digoxin antibody--, these substances were estimated in patients with essential hypertension (EHT), chronic heart failure(CHF), primary and idiopathic hyperaldosteronism(HA), hyperthyroidism(BA) and chronic renal failure(CRF). In EHT, U-DLS, P-DLS, U-ATPI, P-ATPI were significantly higher than those of control(C). In CHF and BA, U-DLS and -ATPI were also significantly higher than those of C. In HA, U-ATPI, DLS distributed in wide range, and a few patients showed high levels of U-DLS and -ATPI. In CRF, P-DLS and -ATPI levels were significantly higher than those of C in prehemodialytic state but P-ATPI was significantly decreased after hemodialysis. From these results it is suggested that 1) DLS and ATPI might contribute to the etiology of hypertension. 2) Volume expansion stimulates the secretion of DLS and ATPI. 3) Stimulatory effect of volume expansion and inhibitory effect of mineralocorticoid may be responsible for wide distribution of these factors in HA. 4) DLS and ATPI are not the same substances.

Topics: Adult; Blood Proteins; Cardenolides; Cardiovascular Diseases; Digoxin; Female; Humans; Hyperaldosteronism; Hypertension; Hyperthyroidism; Kidney Diseases; Male; Middle Aged; Saponins; Sodium-Potassium-Exchanging ATPase

Topics: Calcium; Cystic Fibrosis; Digitalis Glycosides; Digoxin; Heart Diseases; Humans; Hyperaldosteronism; Potassium; Prospective Studies; Saliva